EP 0409181 A3 19910410 - PHOSPHORUS-CONTAINING SQUALENE SYNTHETASE INHIBITORS AND METHOD FOR THEIR PREPARATION
Title (en)
PHOSPHORUS-CONTAINING SQUALENE SYNTHETASE INHIBITORS AND METHOD FOR THEIR PREPARATION
Publication
Application
Priority
US 38143489 A 19890717
Abstract (en)
[origin: EP0409181A2] Compounds which are inhibitors of cholesterol biosynthesis (by inhibiting de novo squalene biosynthesis), and thus are useful as hypocholesterolemic agents and antiatherosclerotic agents are provided which have the structure <CHEM> wherein m is 1, 2 or 3; n is 0, 1, 2 or 3; Y<1> and Y<2> are H or halogen; R<2>, R<3> and R<4> may be the same or different and are independently H, metal ion, C1 to C8 alkyl or C3 to C12 alkenyl; X is O, S, NH or NCH2R<1><5> wherein R<1><5> is H or C1 to C5 alkyl; and R<1> is R<5>-Q<1>-Q<2>-Q<3>- wherein Q<1>, Q<2> and Q<3> are the same or different and are independently <CHEM> a single bond, with the proviso that if Q<1> is a bond, then Q<2> and Q<3> are bonds and if Q<2> is a bond, then Q<3> is a bond, and wherein R<6> is H, alkyl, halo, or haloalkyl, R<7> is H, halo, alkyl or alkylthio; R<8> is H, halogen, trimethylsilyl or lower alkyl; R<9> is H or lower alkyl-; <CHEM> R<1><6>-C IDENTICAL C-CH2- (wherein R<1><6> is H or lower alkyl) or CH3(CH2)p where p is an integer from 2 to 7; R<1><0>, and R<1><1> are the same or different and are independently H, lower alkyl, halogen, haloalkyl or lower alkenyl or R<1><0> and R<1><1> can be taken together to form (CH2)s where s is an integer from 2 to 7; and R<1><3> an R<1><4> are the same or different and are independently lower alkyl, with the proviso that if all of Q<1>, Q<2> and Q<3> are bonds, then both R<1><0> and R<1><1> cannot be H and R<5> cannot be alkyl(CH2)p- with p</=4; including all stereoisomers thereof. New intermediates, new methods of preparation and a method for using such compounds to inhibit cholesterol biosynthesis are also provided.
IPC 1-7
IPC 8 full level
A61K 31/66 (2006.01); A61P 3/06 (2006.01); C07F 9/38 (2006.01); C07F 9/40 (2006.01)
CPC (source: EP KR)
A61P 3/06 (2017.12 - EP); C07F 9/3821 (2013.01 - EP); C07F 9/40 (2013.01 - KR); C07F 9/4012 (2013.01 - EP)
Citation (search report)
- [AE] EP 0324421 A2 19890719 - SQUIBB & SONS INC [US]
- [A] EP 0068732 A1 19830105 - MONSANTO CO [US]
- [A] EP 0189358 A1 19860730 - RHONE POULENC AGROCHIMIE [FR]
- JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 109, no. 18, Sept/Oct 1987, American Chemical Society R.W. MCCLARD et al. "Novel Phosphonyl phosphinyl (P-C-PC-)Analogues of Bio- chemically Interesting Diphosphates. Syntheses and Properties of P-C-PC-Analogues of Isopentyl Disphos- phate and Dimethylallyl Diphosphate" pages 5544-5545, totality.
- THE JOURNAL OF ORGANIC CHEMISTRY, vol. 53, no. 25, 1988, American Chemical Society T.L. CAPSON et al. "Synthesis of Ammonium Analogues of Carbocationic Intermediates in the Guversion of Presqualeue Diphosphate to Squalene" pages 5903-5908, results and discussion; Experimental section.
- JOURNAL OF MEDICINAL CHEMISTRY, vol. 31, no. 10, October 1988 S.A. BILLER et al. "Isoprenoid (Phosphinylmethyl) phosphonates as Inhibitors of Squalene Synynthetase" pages 1869-1871, totality.
Designated contracting state (EPC)
AT BE CH DE DK ES FR GB GR IT LI LU NL SE
DOCDB simple family (publication)
EP 0409181 A2 19910123; EP 0409181 A3 19910410; AU 5900290 A 19910117; AU 635545 B2 19930325; CA 2018470 A1 19910117; HU 210560 B 19950529; HU 904226 D0 19901228; HU T54378 A 19910228; IE 902578 A1 19910227; IL 95052 A0 19910610; JP H0368591 A 19910325; KR 910002882 A 19910226; NZ 234502 A 19940927; ZA 905481 B 19910424
DOCDB simple family (application)
EP 90113700 A 19900717; AU 5900290 A 19900716; CA 2018470 A 19900607; HU 422690 A 19900716; IE 257890 A 19900716; IL 9505290 A 19900712; JP 19186890 A 19900717; KR 900010971 A 19900716; NZ 23450290 A 19900713; ZA 905481 A 19900712